| IED ID | IndEnz0002016548 |
| Enzyme Type ID | protease016548 |
| Protein Name |
Protein AMBP Cleaved into: Alpha-1-microglobulin EC 1.6.2.- ; Inter-alpha-trypsin inhibitor light chain ITI-LC Bikunin HI-30 ; Trypstatin |
| Gene Name | Ambp Itil |
| Organism | Mus musculus (Mouse) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MQGLRTLFLLLTACLASRADPASTLPDIQVQENFSESRIYGKWYNLAVGSTCPWLSRIKDKMSVSTLVLQEGATETEISMTSTRWRRGVCEEITGAYQKTDIDGKFLYHKSKWNITLESYVVHTNYDEYAIFLTKKSSHHHGLTITAKLYGREPQLRDSLLQEFKDVALNVGISENSIIFMPDRGECVPGDREVEPTSIARARRAVLPQESEGSGTEPLITGTLKKEDSCQLNYSEGPCLGMQERYYYNGASMACETFQYGGCLGNGNNFISEKDCLQTCRTIAACNLPIVQGPCRAFIKLWAFDAAQGKCIQFHYGGCKGNGNKFYSEKECKEYCGVPGDGYEELIRS |
| Enzyme Length | 349 |
| Uniprot Accession Number | Q07456 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | BINDING 52; /note=3-hydroxy-L-kynurenine; binds multimeric 3-hydroxykynurenine chromophore; covalent; /evidence=ECO:0000250|UniProtKB:P02760; BINDING 110; /note=3-hydroxy-L-kynurenine; binds multimeric 3-hydroxykynurenine chromophore; covalent; /evidence=ECO:0000250|UniProtKB:P02760; BINDING 136; /note=3-hydroxy-L-kynurenine; binds multimeric 3-hydroxykynurenine chromophore; covalent; /evidence=ECO:0000250|UniProtKB:P02760; BINDING 148; /note=3-hydroxy-L-kynurenine; binds multimeric 3-hydroxykynurenine chromophore; covalent; /evidence=ECO:0000250|UniProtKB:P02760 |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 1.6.2.- |
| Enzyme Function | FUNCTION: [Alpha-1-microglobulin]: Antioxidant and tissue repair protein with reductase, heme-binding and radical-scavenging activities. Removes and protects against harmful oxidants and repairs macromolecules in intravascular and extravascular spaces and in intracellular compartments. Intravascularly, plays a regulatory role in red cell homeostasis by preventing heme- and reactive oxygen species-induced cell damage. Binds and degrades free heme to protect fetal and adult red blood cells from hemolysis. Reduces extracellular methemoglobin, a Fe3+ (ferric) form of hemoglobin that cannot bind oxygen, back to the Fe2+ (ferrous) form deoxyhemoglobin, which has oxygen-carrying potential. Upon acute inflammation, inhibits oxidation of low-density lipoprotein particles by MPO and limits vascular damage. Extravascularly, protects from oxidation products formed on extracellular matrix structures and cell membranes. Catalyzes the reduction of carbonyl groups on oxidized collagen fibers and preserves cellular and extracellular matrix ultrastructures. Importantly, counteracts the oxidative damage at blood-placenta interface, preventing leakage of free fetal hemoglobin into the maternal circulation. Intracellularly, has a role in maintaining mitochondrial redox homeostasis. Bound to complex I of the respiratory chain of mitochondria, may scavenge free radicals and preserve mitochondrial ATP synthesis. Protects renal tubule epithelial cells from heme-induced oxidative damage to mitochondria. Reduces cytochrome c from Fe3+ (ferric) to the Fe2+ (ferrous) state through formation of superoxide anion radicals in the presence of ascorbate or NADH/NADPH electron donor cofactors, ascorbate being the preferred cofactor (By similarity). Has a chaperone role in facilitating the correct folding of bikunin in the endoplasmic reticulum compartment (PubMed:32092411). {ECO:0000250|UniProtKB:P02760, ECO:0000269|PubMed:32092411}.; FUNCTION: [Inter-alpha-trypsin inhibitor light chain]: Kunitz-type serine protease inhibitor and structural component of extracellular matrix with a role in extracellular space remodeling and cell adhesion. Among others, has antiprotease activity toward kallikrein, a protease involved in airway inflammation; inhibits GZMK/granzyme, a granule-stored serine protease involved in NK and T cell cytotoxic responses; and inhibits PLG/plasmin, a protease required for activation of matrix metalloproteinases. As part of I-alpha-I complex, provides for the heavy chains to be transferred from I-alpha-I complex to hyaluronan in the presence of TNFAIP6, in a dynamic process that releases free bikunin and remodels extracellular matrix proteoglycan structures. Free bikunin, but not its heavy chain-bound form, acts as potent protease inhibitor in airway secretions (By similarity). Part of hyaluronan-rich extracellular matrix that surrounds oocyte during cumulus oophorus expansion, an indispensable process for proper ovulation (PubMed:11145954, PubMed:11243855). Also inhibits calcium oxalate crystallization (By similarity). {ECO:0000250|UniProtKB:P02760, ECO:0000269|PubMed:11145954, ECO:0000269|PubMed:11243855}.; FUNCTION: [Trypstatin]: Kunitz-type serine protease inhibitor. Has high catalytic efficiency for F10/blood coagulation factor Xa and may act as an anticoagulant by inhibiting prothrombin activation. Inhibits trypsin and mast cell CMA1/chymase and tryptase proteases. {ECO:0000250|UniProtKB:Q64240}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Binding site (4); Chain (3); Disulfide bond (7); Domain (2); Glycosylation (3); Sequence conflict (2); Signal peptide (1); Site (2) |
| Keywords | Cell membrane;Chromophore;Cleavage on pair of basic residues;Cytoplasm;Disulfide bond;Endoplasmic reticulum;Extracellular matrix;Glycoprotein;Membrane;Mitochondrion;Mitochondrion inner membrane;Nucleus;Oxidoreductase;Protease inhibitor;Reference proteome;Repeat;Secreted;Serine protease inhibitor;Signal |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Alpha-1-microglobulin]: Secreted {ECO:0000250|UniProtKB:P02760}. Endoplasmic reticulum {ECO:0000250|UniProtKB:P02760}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:P02760}. Cell membrane {ECO:0000250|UniProtKB:P02760}; Peripheral membrane protein {ECO:0000250|UniProtKB:P02760}. Nucleus membrane {ECO:0000250|UniProtKB:P02760}; Peripheral membrane protein {ECO:0000250|UniProtKB:P02760}. Mitochondrion inner membrane {ECO:0000250|UniProtKB:P02760}; Peripheral membrane protein {ECO:0000250|UniProtKB:P02760}. Secreted, extracellular space, extracellular matrix {ECO:0000250|UniProtKB:P02760}. Note=The cellular uptake occurs via a non-endocytotic pathway and allows for localization to various membrane structures. A specific binding to plasma membrane suggests the presence of a cell receptor, yet to be identified. Directly binds collagen fibers type I. {ECO:0000250|UniProtKB:P02760}. |
| Modified Residue | |
| Post Translational Modification | PTM: The precursor is proteolytically processed into separately functioning proteins. {ECO:0000250|UniProtKB:P02760}.; PTM: [Alpha-1-microglobulin]: 3-hydroxykynurenine, an oxidized tryptophan metabolite that is common in biological fluids, reacts with Cys-53, Lys-111, Lys-137, and Lys-149 to form heterogeneous polycyclic chromophores including hydroxanthommatin. The reaction by alpha-1-microglobulin is autocatalytic; the human protein forms chromophore even when expressed in insect and bacterial cells. The chromophore can react with accessible cysteines forming non-reducible thioether cross-links with other molecules of alpha-1-microglobulin or with other proteins such as Ig alpha-1 chain C region 'Cys-352'. {ECO:0000250|UniProtKB:P02760}.; PTM: [Inter-alpha-trypsin inhibitor light chain]: Heavy chains are interlinked with bikunin via a chondroitin 4-sulfate bridge to the C-terminal aspartate. {ECO:0000250|UniProtKB:P02760}.; PTM: [Inter-alpha-trypsin inhibitor light chain]: Proteolytically cleaved by PRSS3 at Kunitz domain 2. {ECO:0000250|UniProtKB:P02760}. |
| Signal Peptide | SIGNAL 1..19; /evidence=ECO:0000250 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10337627; 11130978; 11217851; 12204273; 12466851; 1371941; 1385302; 14597629; 15539418; 15576631; 15970507; 16273282; 16331631; 16602821; 17785858; 18554416; 19164299; 19208516; 19302180; 19398962; 20367192; 21267068; 21386911; 22159717; 23157686; 24113769; 28418018; 29987918; 30174180; 30425314; 31740596; 33008134; 7504460; 7508415; 7774911; 7957904; 8611630; 8838309; 8966221; |
| Motif | |
| Gene Encoded By | |
| Mass | 39,029 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |